Characterization and heterologous reconstitution of Taxus biosynthetic enzymes leading to baccatin III
文献类型： 外文期刊
作者： Jiang, Bin 1 ; Gao, Lei 2 ; Wang, Haijun 2 ; Sun, Yaping 1 ; Zhang, Xiaolin 1 ; Ke, Han 2 ; Liu, Shengchao 1 ; Ma, Pengchen 4 ; Liao, Qinggang 1 ; Wang, Yue 1 ; Wang, Huan 1 ; Liu, Yugeng 1 ; Du, Ran 1 ; Rogge, Torben 4 ; Li, Wei 1 ; Shang, Yi 5 ; Houk, K. N. 4 ; Xiong, Xingyao 1 ; Xie, Daoxin 6 ; Huang, Sanwen 1 ; Lei, Xiaoguang 2 ; Yan, Jianbin 1 ;
作者机构： 1.Chinese Acad Agr Sci, Agr Genom Inst Shenzhen, Key Lab Synthet Biol, Shenzhen Branch,Guangdong Lab Lingnan Modern Agr,M, Shenzhen 518124, Peoples R China
2.Peking Univ, Coll Chem & Mol Engn, Key Lab Bioorgan Chem & Mol Engn, Minist Educ,Beijing Natl Lab Mol Sci,Peking Tsingh, Beijing, Peoples R China
3.South China Agr Univ, Coll Life Sci, State Key Lab Conservat & Utilizat Subtrop Agrobio, Guangzhou, Peoples R China
4.Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA USA
5.Yunnan Normal Univ, CAAS YNNU YINMORE Joint Acad Potato Sci, Yunnan Key Lab Potato Biol, Kunming, Peoples R China
6.Tsinghua Univ, Peking Tsinghua Ctr Life Sci, Sch Life Sci, Beijing, Peoples R China
7.Inst Canc Res, Shenzhen Bay Lab, Shenzhen, Peoples R China
期刊名称：SCIENCE （ 影响因子：56.9； 五年影响因子：54.5 ）
ISSN： 0036-8075
年卷期： 2024 年 383 卷 6681 期
页码：
收录情况： SCI
摘要： Paclitaxel is a well known anticancer compound. Its biosynthesis involves the formation of a highly functionalized diterpenoid core skeleton (baccatin III) and the subsequent assembly of a phenylisoserinoyl side chain. Despite intensive investigation for half a century, the complete biosynthetic pathway of baccatin III remains unknown. In this work, we identified a bifunctional cytochrome P450 enzyme [taxane oxetanase 1 (TOT1)] in Taxus mairei that catalyzes an oxidative rearrangement in paclitaxel oxetane formation, which represents a previously unknown enzyme mechanism for oxetane ring formation. We created a screening strategy based on the taxusin biosynthesis pathway and uncovered the enzyme responsible for the taxane oxidation of the C9 position (T9 alpha H1). Finally, we artificially reconstituted a biosynthetic pathway for the production of baccatin III in tobacco.
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